Oral Systemic Therapy Research Articles

Contact Dermatitis in the United States: A Population-Based Study on Patient Visit Characteristics and Treatment Prescription Patterns.

Background: Contact dermatitis (CD) affects ∼15% of the general population over a lifetime. However, there is a lack of epidemiological studies on treatment patterns for CD. Objective: We aim to analyze the patient characteristics and prescribing patterns among dermatologists and general practitioners (GPs) (internal medicine [IM] and family medicine [FM]) for CD in the United States. Methods: We conducted a population-based study using the National Ambulatory Medical Care Survey. Results: We identified 178,017,680 weighted patient visits for CD from 2001 to 2016. Dermatologists saw more white and non-Hispanic patients than GPs. GPs were less likely to prescribe ultrahigh potency topical corticosteroids (FM OR 0.27; P < 0.001, IM OR 0.41; P < 0.001) and more likely to prescribe oral antihistamines (FM OR 3.71; P < 0.001, IM OR 3.56; P < 0.001), oral corticosteroids (FM OR 5.35; P < 0.001, IM OR 6.87; P < 0.001), and injectable corticosteroids (FM OR 3.42; P = 0.006, IM OR 5.68; P < 0.001) than dermatologists. Conclusions: Across CD visits, GPs were less likely than dermatologists to prescribe ultrahigh potency topical corticosteroids and more likely than dermatologists to prescribe oral antihistamines and systemic corticosteroid therapy.

Implementing a drug interaction protocol for oral systemic anti-cancer therapy with focus on CDK4/6 inhibitors.

302 Background: Oral anti-cancer therapies (OACTs) are being increasingly used. Despite their convenience, OACTs introduce challenges with adherence, prescribing errors, and high incidence of drug-drug interactions (DDIs). Currently, there are limited guidelines for DDI checking. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the management of metastatic ER+/HER2- breast cancer. While an overall survival benefit has been demonstrated with Ribociclib, its use can be problematic due to frequent DDIs and the risk of QTc prolongation. DDIs are routinely checked in our center with two interaction checkers, but they are not always documented due to a lack of a standardized protocol. This study aims to evaluate current DDI checking practices, identify common DDIs, and implement a systematic DDI protocol. Methods: A retrospective review was conducted on patients (pts) prescribed CDK4/6i in our center from Jan 2023 to Apr 2024. Data on pt demographics, treatment, DDI documentation, toxicity, and survival were collected. Retrospective DDI checks using Lexi-Interact and Drugs.com were performed. Results: A total of 65 pts were included, with 38 on Ribociclib and 27 on Palbociclib. The median follow-up was 11.6 months (range: 1-71). The median age of pts on Ribociclib was 54 (range: 35-77), compared to 61 (range: 44-82) on Palbociclib. The median number of medications was three with Ribociclib and five with Palbociclib. Seven pts (26%) were prescribed Palbociclib due to contraindications to Ribociclib, including cardiac disease (n=2), QTc-prolonging medications (n=4), and advanced age (n=1). DDI checks were documented in 46% of Ribociclib and 14% of Palbociclib pts (p=0.0063). There was a weak negative correlation between DDI documentation and toxicity, stronger in the Palbociclib arm (-0.079 for Ribociclib vs. -0.335 for Palbociclib). Retrospective checks revealed DDIs in 50% of Ribociclib and 52% of Palbociclib pts. Major DDIs were identified in 21% of Ribociclib and 7% of Palbociclib pts (p=0.133). Common major DDIs involved opioids and QTc-prolonging medications, most frequently antidepressants. Grade ≥3 toxicity occurred in 49% of Ribociclib vs. 64% of Palbociclib pts (p=0.21). Ribociclib caused more rash, liver toxicity, and diarrhea, while Palbociclib had significantly more grade ≥3 neutropenia (48% vs. 21%, p=0.042). No QTc prolongation was observed. Dose reductions were more common with Palbociclib (48% vs. 32%, p=0.27). There was no significant difference in survival data. Conclusions: Our findings highlight the importance of systematic DDI checks in pts receiving OACTs. Implementing a standardized protocol could reduce adverse interactions and improve pt outcomes. Further studies are needed to validate these findings and develop DDI guidelines. A standardized DDI protocol has now been developed for our center, with plans to re-audit after implementation.

Prevalence and Incidence of Psoriatic Arthritis among Patients with Psoriasis and Risk Factors for Psoriatic Arthritis in Republic of Korea: A Nationwide Database Cohort Study.

Population-based epidemiological studies on disease burden and risk factors for psoriatic arthritis (PsA) in patients with psoriasis (PsO) are limited, especially in Asian populations. Therefore, the aim was to determine the prevalence and incidence of PsA among PsO patients in Korea, and examine associated clinical factors. A cohort study was performed to determine the annual prevalence and incidence of PsA among PsO patients between 2008 and 2020 using nationwide claims data in Korea. Risk factors for PsA development were also examined using logistic regression among matched PsA cases and controls. An increasing trend in PsA prevalence per 1,000 patients was observed; prevalence was 6.17 (95% confidence interval [CI] 5.73-6.65) in 2008 and 19.03 (95% CI 18.39-19.70) in 2020. Similarly, the PsA incidence rate per 1,000 patient-years increased from 3.35 (95% CI 3.01-3.72) in 2008 to 5.01 (95% CI 4.68-5.36) in 2020. Patients with plaque PsO, moderate-to severe PsO, receiving oral systemic therapy or phototherapy, with a higher burden of comorbidities, and concomitant autoimmune diseases had a higher risk of PsA. The results provide insight into the burden of PsA among PsO patients in Korea and risk factors associated with developing PsA.

Predictive factors of psoriatic arthritis in a diverse population with psoriasis.

We aimed to analyze the clinical characteristics of patients with psoriasis and determine the predictive factors of psoriatic arthritis (PsA). This retrospective cohort study was performed among patients with psoriasis. Demographic and clinical data were collected. Psoriasis treatment was categorized as topical agents, phototherapy, oral therapy, and biologics. Predictive factors of PsA development were determined using logistic regression analyses. We included 330 patients with psoriasis, and 83 (25%) patients developed PsA. Thirty-eight (45.8%) patients who developed PsA were Malay, 24 (28.9%) were Chinese, and 21 (25.3%) were Indian. The mean age of patients with PsA was 54.2 (±15.8) years, and the duration from diagnosis of psoriasis to diagnosis of PsA was 36 (3.5-114) months. Predictive factors for developing PsA were female sex (odds ratio [OR] = 3.33, 95% confidence interval [CI] 1.78-6.22), presence of nail involvement (OR = 5.36, 95% CI 2.50-11.51), severe psoriasis (OR = 27.41, 95% CI 7.58-99.11), and oral systemic therapy prior to PsA diagnosis (OR = 4.09, 95% CI 2.04-8.22). Patients with psoriasis who are female, have nail involvement, severe skin psoriasis, and require oral systemic therapy for psoriasis may have an increased risk of developing PsA.

Complete Remission of Cutaneous Metastasis from Invasive Breast Cancer with Abemaciclib plus Letrozole

AbstractSkin metastases from internal malignancies can be the first clinical finding of cancer recurrence. If presentation is delayed, they may ulcerate and develop secondary infection. Through this case, we will highlight a case of breast cancer recurrence with extensive cutaneous metastases that clinically completely responded to oral systemic therapy, thereby obviating the need for chemotherapy and leading to stark improvement in performance status and quality of life.

Efficacy and safety of abrocitinib in patients with moderate‐to‐severe atopic dermatitis with prior exposure to oral systemic immunosuppressants or biologic therapies: A post hoc analysis of the JADE clinical trials

AbstractBackgroundPatients with moderate‐to‐severe atopic dermatitis (AD) refractory to topical therapy might require treatment with systemic therapies, including biologics.ObjectivesTo assess the efficacy and safety of abrocitinib monotherapy in patients who previously received systemic therapies.MethodsThis post hoc analysis included patients receiving abrocitinib (200 mg/100 mg) or placebo in the phase 2b and phase 3 JADE MONO‐1 and MONO‐2, REGIMEN (abrocitinib 200 mg; open‐label period) and EXTEND (patients enrolled from MONO‐1 and MONO‐2) trials. Patients who were systemic therapy‐naive or had received prior oral systemic or biologic therapies were assessed for Investigator's Global Assessment (IGA) response of 0 (clear) or 1 (almost clear) and ≥2‐point improvement from baseline, ≥75% or ≥90% improvement in Eczema Area and Severity Index (EASI‐75 or EASI‐90), ≥4‐point improvement in Peak Pruritus Numerical Rating Scale (PP‐NRS4), PP‐NRS score of 0 or 1 and change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) and Patient‐Oriented Eczema Measure (POEM) scores. Safety was assessed.ResultsThis analysis included 1579 patients (systemic therapy‐naive, n = 997; prior exposure to oral systemic, n = 429; biologic therapies, n = 153). At Week 12, IGA 0/1 response rates (95% confidence intervals) among patients who were systemic therapy‐naive, had received prior oral systemic therapy or had received biologic therapy were 44.4% (37.5–51.4), 34.5% (22.3–46.7) and 43.5% (23.2–63.7) with abrocitinib 200 mg, 30.9% (24.2–37.5), 16.4% (7.1–25.7) and 24.1% (8.6–39.7) with abrocitinib 100 mg and 9.6% (4.2–14.9), 5.9% (0.0–13.8) and 0.0% (0.0–23.2) with placebo in the pooled monotherapy trials; and 67.0% (62.8–71.2), 62.2% (56.4–68.0) and 53.5% (42.9–64.0) in REGIMEN. Across subgroups, abrocitinib showed greater improvement in EASI‐75, PP‐NRS4, EASI‐90, PP‐NRS 0/1, PSAAD and POEM scores versus placebo. Similar results were seen at Week 48. No new safety signals were observed.ConclusionsPrior use of oral systemic or biologic therapies did not seem to impact the efficacy and safety of abrocitinib in patients with moderate‐to‐severe AD.

P35 Adopting a personalized approach to blood monitoring in patients with psoriasis-prescribed biological therapy: a retrospective single-centre review of real-world data

Abstract Six-monthly blood monitoring is performed for patients with psoriasis-prescribed biological drugs at most UK centres. This has significant healthcare cost implications, creates a burden on patient time and has a considerable environmental impact. We aimed to investigate blood abnormalities in patients prescribed biologics in our centre, to determine whether the monitoring frequency could be reduced. We reviewed the records of patients with psoriasis prescribed a biologic drug who attended the clinic between September and October 2022 and collected blood result data from the preceding 2 years. Normal ranges were determined by electronic health record ranges. In total, 102 patients were included (male : female ratio 47 : 55, median age 48.5 years). Adalimumab (n = 39), ustekinumab (n = 36) and risankizumab (n = 13) were the most prescribed biologics. Ten patients were prescribed oral systemic therapy (six methotrexate and four acitretin). The median blood monitoring interval was 5 months. Overall, blood abnormalities were present in 38 of 102 patients (37.2%). Transaminitis was most common (n = 23, all ≤ 80 U L−1): ten had documented liver disease and two were coprescribed methotrexate. Two patients had abnormalities requiring immediate retesting (acute kidney injury and new anaemia) and 36 had mild abnormalities. Fourteen patients had developed abnormalities since commencing biologic therapy [neutrophilia, n = 2; neutropenia, n = 1 (adalimumab); lymphopenia, n = 1 (ustekinumab); transaminitis, n = 8; thrombocytosis, n = 2; thrombocytopenia, n = 1; anaemia n = 1; low urea, n = 1; raised creatinine, n = 1]. Despite abnormalities present in 37% of patients, the majority were mildly deranged and only 14 patients developed the abnormality after commencing biologic therapy. Many of these patients have multiple long-term conditions, monitored in other clinics. None of the blood abnormalities detected was directly attributed to commencing the biologic or prompted stopping biologic therapy. Our data support that a more targeted and coordinated approach to blood monitoring could be adopted and should be formally assessed. Applying sustainable healthcare coalition and government vehicle emission figures to findings from a survey of patients with psoriasis prescribed a biologic in our department, we estimate an annual carbon saving of &amp;gt; 850 kg CO2 equivalents (CO2e) for patient travel alone if monitoring for patients with no specific risk factors became annual. When considering addition factors, such as building energy and consumables disposal, this saving could rise to &amp;gt; 6400 kg CO2e. Up to 60% of patients miss work to attend appointments and, for a minority, earnings are consequently lost (outpatient survey data). Evidently, more targeted monitoring could substantially reduce carbon emissions, disruption to employment and associated healthcare costs. Further evaluation through larger studies is required to ensure ongoing safe prescribing with personalized blood monitoring.

ORAL MICROBIOME SEQUENCING TEST IN A CLINICAL CASE OF ACUTE MYELOID LEUKEMIA WITH PERSISTENT ORAL INFECTION

A previously healthy, 45-year-old female patient, with the recurrence of acute myeloid leukemia, was hospitalized for oncological treatment. During hospitalization, she presented episodes of febrile neutropenia associated with pharyngotonsillitis and thrombocytopenia. Oral clinical examination presented erythematous and swollen gums with active bleeding. Thus, mechanical and chemical local control of the oral microbiota and systemic antibiotic therapy were instituted. Three conclusive cultures of gingival secretion were performed, which was conclusive for normal oropharyngeal microbiota; however, the infection panorama is still persistent. An oral microbiome DNA from saliva test was performed, resulting in 167027 sequences harboring 34 types of bacteria. Among the identified microorganisms, Granulicatella adiacens and Veillonella parvula were found in greater quantity, which could be responsible for oral homeostasis instability. Two days after the oral microbiome test result, the patient died. A previously healthy, 45-year-old female patient, with the recurrence of acute myeloid leukemia, was hospitalized for oncological treatment. During hospitalization, she presented episodes of febrile neutropenia associated with pharyngotonsillitis and thrombocytopenia. Oral clinical examination presented erythematous and swollen gums with active bleeding. Thus, mechanical and chemical local control of the oral microbiota and systemic antibiotic therapy were instituted. Three conclusive cultures of gingival secretion were performed, which was conclusive for normal oropharyngeal microbiota; however, the infection panorama is still persistent. An oral microbiome DNA from saliva test was performed, resulting in 167027 sequences harboring 34 types of bacteria. Among the identified microorganisms, Granulicatella adiacens and Veillonella parvula were found in greater quantity, which could be responsible for oral homeostasis instability. Two days after the oral microbiome test result, the patient died.

Real-world treatment patterns and healthcare costs in patients with psoriasis taking systemic oral or biologic therapies

BackgroundPsoriasis is a chronic, immune-mediated, systemic inflammatory disorder associated with high costs. This study evaluated real-world treatment patterns and associated costs in patients in the United States with psoriasis initiating systemic oral or biologic treatments.MethodsThis retrospective cohort study used IBM® (now Merative™) MarketScan® Commercial and Medicare claims (1 January 2006–31 December 2019) to evaluate patterns of switching, discontinuation, and nonswitching in two cohorts of patients initiating oral or biologic systemic therapy. Total pre-switch and post-switch costs were reported per-patient per-month (PPPM).ResultsEach cohort was analyzed (oral, n = 11,993; biologic; n = 9753). Among the oral and biologic cohorts, 32% and 15% discontinued index and any systemic treatment within 1 year of initiation; 40% and 62% remained on index therapy; and 28% and 23% switched treatment, respectively. In the oral and biologic cohorts, total PPPM costs within 1 year of initiation for nonswitchers, patients who discontinued, and patients who switched were $2594, $1402, and $3956, respectively, and $5035, $3112, and $5833, respectively.ConclusionThis study identified lower persistence in the oral treatment cohort, higher costs associated with switching, and a need for safe and effective oral treatment options for patients with psoriasis to delay the switch to biologic therapy.

Psoriasis Clearance Rates with Different Treatments – An In-depth Retrospective Chart Review

Abstract Background: Before the advent of biologics, psoriasis clearance was not a realistic goal of treatment. Purpose: This retrospective chart review aimed to compare the rates of psoriasis clearance associated with different modes of therapy in real-life practice. Methods: The study included 256 psoriasis patients who had &gt;2 Physician Global Assessment and body surface area scores and psoriasis treatments recorded during a 3-year period. Results: Injection biologics performed better than regimens including topical agents alone or in combination with topical and oral systemic therapy. Patients on injection regimens accounted for 90% of patients with disease clearance. Injection therapy alone had a larger decrease in psoriasis severity scores from baseline than injection therapy combined with other agents. Despite clinical trials being monotherapy studies, this study conducted at a large referral center aligns with the clearance rates reported in clinical trials. Conclusion: Our results suggest that monotherapy studies can be translated into community practice. Overall, this study adds to the growing body of evidence supporting the use of biologic therapy in psoriasis management and underscores the importance of patient education on the potential for complete clearance with modern therapies.

Exudative retinal detachment and optic disc swelling in the course of posterior scleritis: case study and literature review

Objectives: The objective of the present paper is to present a rare case of posterior scleritis with exudative retinal detachment and optic disc oedema.&#x0D; Materials: The paper discusses a case of a 28-year-old patient with unilateral posterior scleritis, exudative retinal detachment and optic disc oedema. The patient presented with reduced visual acuity and inflammation within his right eyeball coat.&#x0D; Test results: Upon admission, retinal detachment in all quadrants was diagnosed, with subretinal exudate, choroidal folds, but no pathology involving the anterior segment. B projection ultrasound revealed thickening of the posterior sclera of around 2.0 mm and complete retinal detachment in the right eye. Visual acuity results were OD = 1/50 Sc, OS = 45/50 Sc. Elevated intraocular pressure of the right eye was detected at 44.0 mmHg A CT scan of the orbits with contrast revealed significant asymmetry of the eyeballs (right 22 × 22 mm, left 21 × 21 mm) as well as posterior thickening of the right eyeball coat to 2.0 mm. On top of that, on the second day of the patient’s hospital stay, an ophthalmic exam showed obscured borders of the right optic nerve. Systemic treatment was initiated, comprising steroids, non-steroidal anti-inflammatory drugs and intraocular pressure lowering drugs. Additionally, topical treatment was provided with regard to the right eye. A number of laboratory tests were carried out to rule out systemic diseases that could have caused posterior scleritis. After discharge, the patient received follow up care from the hospital’s ophthalmology clinic and remained on topical and systemic steroids. Oral systemic steroid therapy was maintained over a period of a few months, with gradual dose reduction. At follow-up visits, his visual acuity remained stable at OD = 40/50 Sc, OS = 45/50 Sc.&#x0D; Conclusions: Posterior scleritis is a condition that requires prompt diagnosis and systemic treatment.

A mixed-methods study to identify key priorities around improving team-based care coordination for patients receiving combination IV and oral systemic anti-cancer therapy.

52 Background: When combination medical therapy incorporates both IV and oral anti-cancer agents, patients may experience compound side effects and face challenges with treatment adherence. To assess how community cancer programs may improve care coordination for patients receiving combination IV/oral systemic therapy, the Association of Community Cancer Centers (ACCC) conducted a mixed-methods study that involved healthcare professionals (HCPs), patients and caregivers. Methods: The study followed a sequential quantitative-qualitative design to answer questions around the barriers or challenges associated with combination IV/oral systemic therapy. The quantitative phase included an online survey of HCPs (by ACCC) and a survey of patients and caregivers (by Edge Research, in collaboration with several patient advocacy organizations). In the quantitative phase, the survey results were contextualized through two HCP focus groups and individual HCP interviews. Results: Comparing and contrasting the patient survey (n = 113) and HCP survey (n = 157) results revealed insights around the following themes: Top Challenges: Patients felt their top challenges were side effects (57.5%); inconvenience going to medical appointments (37.2%); and financial burden (36.3%). HCPs perceived top challenges as cost of care to the patient (24.0%); coordination and delivery of oral agents (22.1%); and health insurance coverage (21.9%). In focus groups, HCPs explained how they were investing significant staffing resources to prevent and mitigate financial toxicity, especially for patients receiving oral therapies. Methods of Communication: 35.4% of patients “highly preferred” using email to communicate with HCPs about their combination regimens. However, HCPs felt that email was one of the least effective methods of communicating with patients. In focus groups, HCPs agreed that email is convenient when communicating about non-urgent matters. However, they were concerned that some patients may use email to communicate about urgent issues. Treatment-related AEs: When patients experienced treatment-related AEs, 30.1% said their clinicians tried a dose modification or hold. HCPs had mixed perceptions regarding the effectiveness of dose holidays. Those who felt this was highly effective included: advanced practice providers (42.9%), nurses (28.1%); oncologists (16.7%); and pharmacists (16.7%). Conclusions: This study identifies opportunities to improve care coordination for patients receiving combination IV/oral systemic anti-cancer regimens. These findings may inform the creation and dissemination of effective practices and quality improvement projects. These results may also help cancer programs tailor resources and incorporate proactive steps to address some of the key challenges patients may face.

Oncological Care During First Peruvian National Emergency COVID-19 Pandemic: A Multicentric Descriptive Study.

PurposeThe aim of this study is to evaluate the oncological care during the first state of national emergency due to the COVID-19 pandemic in several public cancer hospitals in Peru.Materials and MethodsA multicentric cross-sectional descriptive study was conducted by interviewing adult cancer patients diagnosed and treated between January 2019 and February 2020 from 18 hospitals. This study was carried out in September 2020, the last month of the first state of national emergency. Demographic and clinical characteristics were evaluated, including COVID-19 status and cancer treatment features.ResultsA total of 1472 patients were included; the median age was 55 years (range 19–97). Most patients (85.8%, n = 1263) had solid neoplasia, 13.5% (n = 198) hematologic neoplasia, and 0.7% (n = 11) others. SARS-CoV-2 infection was confirmed in 8.6% (n = 126), 1.2% (n = 18) were probable, 1.6% (n = 24) suspected, and 88.6% (n = 1304) negative cases. Overall, 51.6% of patients (n = 759) had cancer treatment delays, 42.5% (n = 626) changed treatment delivery (endovenous to oral systemic therapy), and 12.6% (n = 185) of cases cancer therapy was discontinued. In total, 10.3% (n = 117) of patients whose disease was controlled or in remission, experienced progression of disease during the state of emergency. A total of 6.7% (n = 98) of patients died, of whom 73.5% (n = 72) died from disease progression; 18.4% (n = 18) from SARS-CoV-2 infection and 8.1% (n = 8) from undetermined causes. Patients with hematological malignancies [hazard ratio (HR): 5.11 (95% confidence interval (CI): 1.99–13.07)] and no response to therapy before the onset of the pandemic [5.01 (1.44–17.42)] had an increased risk of death among COVID-19 infected individuals, whereas advanced clinical stage [5.09 (2.37–10.95)] and discontinuation of treatment [3.66 (1.97–6.78)] were risk factors among non-COVID-19 patients.ConclusionOur study suggests that the COVID-19 pandemic has an adverse impact on the outcomes of Peruvian cancer patients. In our cohort, cancer mortality was higher than COVID-19 disease mortality.

Temporal Outcomes after Rituximab Therapy for Pemphigus Vulgaris

Pemphigus vulgaris is an autoimmune blistering disease characterized by autoantibodies that target desmoglein adhesion proteins. Rituximab and corticosteroids are Food and Drug Administration‒approved therapies for pemphigus vulgaris. As newer treatments for pemphigus enter clinical trials, analysis of clinical and serologic outcomes after rituximab therapy as a function of time is essential to guide clinical trial design. In this study, we report detailed temporal and serologic outcomes of rituximab treatment of pemphigus vulgaris. The maximal prevalence of complete remission off oral systemic therapy after a single cycle of rituximab was 32.4% at 12 months or 43.1% by 36 months, including additional rituximab cycles. Using receiver operating characteristic curves to develop prediction models for complete remission after a single cycle of rituximab, >90.7% reduction in average desmoglein 3 ELISA titers from baseline to months 3‒9 was 94% sensitive, and an average absolute titer ≤130 RU/ml between months 3 and 9 was 96% specific, for achievement of complete remission off oral systemic therapy. All patients with negative titers at 6‒9 months ultimately achieved complete remission off oral systemic therapy. This dataset of clinical and serologic outcomes for patients with pemphigus vulgaris after rituximab therapy will facilitate clinical trial planning and also guide clinician and patient expectations after rituximab therapy.

Systematic review of sirolimus in dermatological conditions.

Sirolimus is a mammalian target of rapamycin inhibitor (mTORI) with anti-proliferative, antiangiogenic and immunosuppressive properties. While approved in Australia as an anti-rejection medication for renal transplant patients, there is mounting evidence regarding the utility of oral and topical sirolimus in treating a plethora of dermatological conditions or conditions with cutaneous manifestations. Our aim was to present an overview of the evidence for current usage and breadth of the application of sirolimus in dermatology. We carried out a systematic review of all the literature published up to 31 August 2019 on oral and topical sirolimus with respect to dermatological conditions or conditions otherwise relevant to dermatology. While 3368 papers were initially produced in our search, 238 papers met our inclusion criteria and were examined in our review. The conditions examined were categorised into genodermatoses (9 conditions), infection (1 condition), inflammatory/autoimmune (10 conditions), neoplasm (3 conditions) and vascular (17 conditions). We extracted data on first author, publication year, journal, characteristics of the study and study patients, condition, drug modalities, drug efficacy, side effects, blood level of mTORI, co-interventions and follow-up. While there is level 1 evidence for the efficacy of sirolimus in conditions such as tuberous sclerosis complex (TSC) and GVHD prophylaxis, for many other conditions, the evidence is limited to level 4 evidence. Regarding oral systemic therapy, dosing regimens varied with the most common for children 0.8mg/m2 twice daily and for adults 1 mg twice daily. Doses were often adjusted to reach a typical trough level of between 5 and 15 ng/mL, though targets often varied. In the overall majority of cases, side effects were minimal or tolerable, including mucositis, cytopenias, lipid abnormalities and nausea/vomiting, and only a few cases had to stop due to adverse effects. Regarding topical therapy, concentration of formulations varied from 0.1% to 1% and were compounded into creams, ointments or gels and administered typically once or twice per day. The most common side effect was skin irritation. There were a number of limitations to our study. In particular, many of the published studies were case reports or case series with no comparator arm, leading to susceptibility of bias in conclusions drawn, in particular a high likelihood of publication bias. Given the heterogeneity amongst studies, comparisons or aggregation of results was difficult. There continues to be growing use of oral and topical sirolimus in dermatological conditions. It provides new therapeutic options to patients where previous therapies have either failed or are limited due to toxicity. However, further studies are warranted.

Real-World Outcomes of Advanced Soft Tissue Sarcoma Patients Treated with Pazopanib

Background: Pazopanib is an oral multitarget tyrosine kinase inhibitor that is currently approved for the treatment of select subtypes of advanced Soft Tissue Sarcoma (STS) in patients who have progressed on prior anthracyclinebased chemotherapy regimens. In this study, we examine data from multiple centers to assess the efficacy of pazopanib in practice outside of a clinical trial setting. Methods: A retrospective chart analysis was conducted for pre-treated, advanced soft tissue sarcoma patients who began treatment with pazopanib in Alberta, Canada and Cairo, Egypt (2012-2018). Results: In total, 39 predominantly male (56.4%) patients received pazopanib. The median age was 51, 67% of whom had an ECOG of one or less. The predominant sarcoma subtype was leiomyosarcoma (30.8%), and all patients had received at least one prior line of systemic therapy. Thirtytwo of the 39 patients (82%) were initially given the full dose of 800mg with a median time on treatment of 116 days. Seven of the 39 (18%) patients required a dose reduction while on treatment. A majority (94.9%) of patients ultimately discontinued pazopanib treatment for reasons including death (21.6%), disease progression (62.2%), and toxicity (16.4%). The median progression-free and overall survival for these patients was 4.1 months (95%CI, 3.6-4.5) and 8.4 months (95% CI, 4.3-12.5), respectively. Conclusion: Pazopanib is an efficient and generally well-tolerated oral systemic therapy for the treatment of advanced, pre-treated, non-adipocytic soft tissue sarcoma. These results show the efficacy of pazoponib outside of a clinical trial setting.

A Population-based Study Comparing Outcomes for Patients With Metastatic Castrate Resistant Prostate Cancer Treated by Urologists or Medical Oncologists With First Line Abiraterone Acetate or Enzalutamide

ObjectivesTo compare toxicity and all-cause mortality for mCRPC patients receiving first line oral systemic therapy prescribed by medical oncologists and urologists. MethodsPopulation-based retrospective cohort study of chemotherapy-naïve men aged ≥66 years treated for mCRPC with first-line abiraterone or enzalutamide based on administrative health data (Ontario, Canada, 2012-2017). Primary outcomes were hospitalizations/ER visits for any cause or treatment-related toxicity during first-line mCRPC treatment. Secondary outcome was all-cause mortality. We calculated hazard ratios (HRs) comparing outcomes for different medical specialties using multivariable Cox proportional hazards models. ResultsAmong 3405 mCRPC patients, 2407 (70.7%) received abiraterone and 998 (29.3%) received enzalutamide. 1786 (52.5%) patients visited the ER or were hospitalized. Men treated by medical oncologists had an increased risk of hospitalization/ER visits (HR1.16, 95%CI 1.03-1.31; P = .02), toxicity-related visits (HR1.34, 95%CI 1.08-1.69; P = .01), and mortality (HR1.16, 95%CI 1.02-1.33; P = .02) compared to urologists. Limited information was available, beyond PSA adjustment and prior treatment, on patient disease burden. ConclusionWe observed fewer hospital visits overall and for treatment-related toxicity for mCRPC patients who were prescribed first line abiraterone or enzalutamide by urologists compared to medical oncologists. These differences may result from higher prostate cancer disease burden in patients managed by medical oncologists, and/or other unmeasured differences in patient management between specialties.

Gaps in moderate plaque psoriasis management: A survey of Saudi dermatologists.

Background:There are many barriers that usually lead to under-treatment of moderate psoriasis patients, with subsequent unsatisfactory results and clinical outcomes.Objective:Given this lack of consistent guidelines on treating moderate plaque psoriasis patients, the aim of the current study is to define how Saudi dermatologists define and treat such cases in the real-world clinical setting.Methods:We conducted an online cross-sectional survey from May 2020 to October 2020, involving all eligible dermatologists working at different academic, governmental, and private sectors in Saudi Arabia.Results:Finally, a total of 260 dermatologists were included in the final analysis; out of them, 140 (53.8%) were males and 120 (46.2%) were females. Regarding the tools used by participating dermatologists for diagnosis of moderate psoriasis, most of the participants (86.5%) used Body Surface Area (BSA), 7.3% used Physician Global Assessment (PGA), and 6.2% used Dermatology Life Quality Index (DLQI). Cutoff scores for defining moderate psoriasis varied widely among surveyed dermatologists. The surveyed dermatologists reported that 46% of their patients with moderate plaque psoriasis were receiving biologics as their primary therapy, while 24.1% were receiving prescription topical treatment, 20.3% were receiving an oral systemic therapy, 4.9% were using over-the-counter topical treatment, and 4.7% were receiving phototherapy.Conclusion:There is a pervasive lack of consensus regarding the definition of moderate psoriasis, with reported wide ranges among the commonly used severity tools in psoriasis patients.

COVID-19 and financial toxicity in patients with renal cell carcinoma

PurposeTo ascertain renal cell carcinoma (RCC) financial toxicity on COVID-19 during the COVID-19 crisis as patients are struggling with therapeutic and financial implications.MethodsAn online survey was conducted from March 22 to March 25, 2020. It included baseline demographic, clinicopathologic, treatment-related information, anxiety levels related to COVID-19, questions related to financial concerns about COVID-19 as well as the validated 11-item COST measure.ResultsFive-hundred-and-thirty-nine patients (39%:58% male:female) from 14 countries responded. 23% of the patients did not feel in control of their financial situation but 8% reported being very satisfied with their finances. The median COST score was 21.5 (range 1–44). Metastatic patients who have not started systemic therapy had a COST score (19.8 range 2–41) versus patients on oral systemic therapy had a COST score (23.9 range 4–44). Patients in follow-up after surgery had a median COST score at 20.8 (range 1–40). A low COST scores correlated (p < 0.001) were female gender (r = 0.108), younger age (r = 0.210), urban living situation (r = 0.68), a lower educational level (r = 0.155), lower income (r = 0.165), higher anxiety about acquiring COVID-19 (r = 0.198), having metastatic disease (r = 0.073) and a higher distress score about cancer progression (r = 0.224).ConclusionOur data highlight severe financial impact of COVID-19. Acknowledging financial hardship and thorough counseling of cancer patients should be part of the conversation during the pandemic. Treatment and surveillance of RCC patients might have to be adjusted to contemplate financial and medical needs.

Improving the quality of oral cancer drug delivery across a health system.

184 Background: Oral systemic therapy (ST) presents unique care delivery challenges. Gaps in patient education and monitoring for patients on oral ST delivery are well documented and can result in decreased adherence or increased toxicity. Within Ontario, cancer care is provincially coordinated through Ontario Health- Cancer Care Ontario (OH-CCO), but locally implemented by 14 Regional Cancer Programs (RCPs). Using a centrally coordinated, but regionally implemented quality improvement (QI) approach, we aimed to improve the quality of oral ST delivery across Ontario by enabling the use of patient specific monitoring plans to optimize treatment adherence and toxicity management. Methods: Between 2018 and 2020 a 2 year focused QI project was undertaken. A suite of 19 quality measures were developed to measure different quality domains for oral ST delivery including treatment plan documentation, patient education, toxicity/adherence monitoring and toxicity outcomes. In year 1, all regions used the suite of quality measures to establish baseline performance and develop a QI plan using rapid cycle improvement methodology to improve performance in at least 1 domain based on regional gaps and priorities. Projects were implemented and evaluated during year 2. OH-CCO provided QI coaching through dissemination of standardized QI tools, a monthly discussion forum and project specific feedback. At the end of year 2, a post-implementation evaluation was performed for each region. Results: 15 centers participated, representing all RCPs across Ontario. The participating centers implemented QI projects focused on treatment plan documentation (N = 3), patient education (N = 10) and toxicity/adherence management (N = 5), with some focusing on multiple domains. All centers reported an improvement in at least 1 domain (see Table). Key enablers identified include engagement with a multi-disciplinary team and the use of technology, while barriers include lack of onsite dispensing pharmacy. Future work will continue to focus on quality of oral ST delivery and better pharmacy integration. Conclusions: Through a centrally coordinated, locally implemented QI project, improvement in quality of oral ST care was achieved across Ontario. This model of QI focus has the potential to be adaptable across health systems. [Table: see text]